诱导白色脂肪棕色化的靶向递送载体的研究进展  

Advances of targeted delivery vectors for inducing browning of white adipose tissue

作　　者：孙倩雯 许雅琪 陈微 叶军[1] 王洪亮[1] 高丽丽 高越 刘玉玲[1] 杨艳芳 SUN Qian-wen;XU Ya-qi;CHEN Wei;YE Jun;WANG Hong-liang;GAO Li-li;GAO Yue;LIU Yu-ling;YANG Yan-fang(Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China)

机构地区：[1]中国医学科学院、北京协和医学院药物研究所,北京100050

出　　处：《药学学报》2022年第7期2049-2056,共8页Acta Pharmaceutica Sinica

基　　金：国家重大新药创制科技重大专项(2018ZX09721003);北京市自然科学基金资助项目(7212155);中国医学科学院医学与健康科技创新工程(CIFMS-2021-I2M-1-026)。

摘　　要：肥胖已成为糖尿病和内分泌紊乱等疾病的重要诱导因素,抗肥胖治疗也成为研究热点。抑制脂肪合成并促进脂肪分解是药物抗肥胖治疗的重要方式,随着对机体脂肪组织分布、形态和功能的深入研究,含有多腔室脂滴和丰富线粒体的棕色脂肪组织引起了人们关注。此外,一种与棕色脂肪细胞形态和功能相似的米色脂肪细胞也引起了人们极大的兴趣,该类细胞可在外界刺激或褐变剂诱导下由白色脂肪细胞转化而来,称为“白色脂肪棕色化”。在此过程中,细胞内促能量消耗的蛋白表达增加,使脂肪细胞功能由储能转为耗能,从而增加体内过多能量消耗,减少脂质堆积,因此,诱导白色脂肪组织棕色化为治疗肥胖带来了新思路。但褐变剂的系统给药存在对非靶组织如心脏、中枢神经系统等产生不良反应的风险,限制了其在诱导白色脂肪棕色化中的应用。通过构建靶向白色脂肪组织的药物递送系统实现褐变剂靶向给药可降低其不良反应,提高生物利用度。本文将从白色脂肪棕色化的机制、常用褐变剂及诱导白色脂肪组织棕色化的靶向递送载体等方面进行全面综述。Obesity has become an important inducer of many public diseases such as diabetes,endocrine disorders,and so on.Anti-obesity treatment has become a hot topic.Inhibiting fat synthesis and promoting fat decomposition are important ways of drug anti-obesity treatment.With the in-depth study of the distribution,morphology and function of adipose tissue,brown adipose tissue containing multi-compartment fat drops and rich mitochondria have attracted people’s attention.Beige adipocytes which are similar to brown adipocytes in morphology and function have aroused great interest,such cells can be transformed from white adipocytes by external stimulation or browning agents.This process is called"white fat browning".The expression of promoting energy consumption proteins in these cells increase,so that the function of adipocytes changes from energy storage to energy consumption to increase excessive energy consumption in the body and reduce lipid accumulation.The browning of white adipose tissue has brought new ideas for obesity treatment,but the systemic administration of browning agent has the risk of adverse reactions to non-target tissues such as heart and central nervous system,which limits its application in inducing white fat browning.Browning agents to white adipose tissue can reduce its adverse reactions and improve its bioavailability by constructing a drug delivery system targeting white adipose tissue.In this review,the mechanism on browning of white adipose tissue,the commonly used browning agents and the targeted delivery carriers that induce browning of white adipose tissue are summarized.

关 键 词：肥胖 白色脂肪棕色化 褐变剂 机制 靶向递送 

分 类 号：R943[医药卫生—药剂学]